POS0867 B-CELL SUBSETS IN PERIPHERAL BLOOD ACROSS DISEASE PHASES OF PSORIATIC ARTHRITIS AND THEIR CORRELATION WITH SYNOVIAL TISSUE FEATURES
Authors: D. Bruno, B. Tolusso, C. DI Mario, S. Perniola, D. Somma, L. Petricca, A. Chiricozzi, M. R. Gigante, A. D’amore, M. Kurowska-Stolarska, S. Alivernini, E. Gremese
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Psoriatic Arthritis (PsA) has been historically considered as a T-cell driven disease, with the role of B-cells generally under investigated since common seronegativity. However, over the years new insights have come to light on B-cells in PsA, focusing on the presence of ectopic lymphoid structures as well as on the presence of specific anti-carbamylated/citrullinated cathelicidin LL37 antibodies in psoriatic SF and plasma. <h3>Objectives</h3> The aim of the study was to examine the frequencies of distinct peripheral blood (PB) B-cell subsets in across different disease phases, evaluating their potential correlation with synovial tissue (ST) heterogeneity in terms of inflammatory degree and microanatomical organization. <h3>Methods</h3> 150 patients fulfilling the CASPAR criteria for PsA were recruited (81 naive to cDMARDs or bDMARDs, 45 c- and/or b-DMARDs resistant and 24 in clinical and US sustained remission, respectively) and underwent US-guided ST biopsy and PB withdrawal. 22 patients with psoriasis (PsO) and arthralgia were included as comparison group. All ST FFPE specimens were routinely processed and stained with H&amp;E and classified by a pathologist, blinded to clinical characteristics, using a H&amp;E based semiquantitive score (KSS) integrated with the presence/absence of lymphocytes, plasmacells, granulocytes and myxoid degeneration, respectively. [1] Frequencies of PB B-cell subpopulations were determined by FACS using the CD27/IgD classification as follows: naïve B-cells (CD27<sup>neg</sup>IgD<sup>pos</sup>), IgM memory (CD27<sup>pos</sup>IgD<sup>pos</sup>), switched memory (CD27<sup>pos</sup>IgD <sup>neg</sup>), late memory (CD27 <sup>neg</sup>IgD <sup>neg</sup>), plasmablasts (CD27<sup>pos</sup>CD38<sup>pos</sup>) and plasmacells (CD138<sup>pos</sup>). <h3>Results</h3> In PsA cohort, the distribution of synovitis score was significantly different among patients with distinct disease phases (ANOVA p&lt;0.001). In particular, KSS was contingent on disease phase being significantly lower in PsA in remission (2.04 ± 1.39) compared to naive (3.20 ± 1.77, p=0.02) and resistant PsA (3.78 ± 2.22, p&lt;0.001), while there was no significant difference between remission PsA and at risk PsO group in terms of synovial hyperplasia, stromal density, and lymphocyte infiltrate respectively. ST of c- and/or b-DMARDs resistant PsA was enriched of plasmacells than remission PsA (p=0.03). Considering B-cell subpopulations, PB of c- and/or b-DMARDs resistant PsA was enriched of plasmablasts and plasmacells compared to PsO at risk of PsA development (p=0.01 for plasmablasts and p=0.001 for plasmacells, respectively). Conversely, c- and/or b-DMARDs resistant PsA showed, at PB level, lower rates of switched memory and naïve B-cells compared to PsO at risk of PsA development (p= 0.02 for switched memory and p=0.039 for naive, respectively). Finally, stratifying PsA based on KSS category, remission PsA with persistent high grade synovitis (KSS ≥ 5) showed lower rates of PB plasmablasts compared to remission PsA with low grade or without residual synovial inflammation (p=0.045). <h3>Conclusion</h3> Disease state across PsA course significantly impacts PB B-cell subsets distribution mirroring ST residual inflammation at the time of sustained disease remission and supporting the tight dynamic connection between PB and ST environments. <h3>Reference</h3> [1]Alivernini S et al. Arthritis &amp; Rheumatology 2021 <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.